This invention relates to the in vitro production of collagenase inducing factor from the human liver adenocarcinoma cell line SK-HEP-1.
Collagenase is a proteolytic enzyme which acts on the protein collagen. The natural substrate collagen constitutes the connective tissue of the body and is the major type of fibrous protein in higher vertebrae, including mammals. In man, approximately one-third of the total protein content is collagen. The ability of collagenase to digest native collagen provides the enzyme with a variety of uses in tissue culture and cell studies including the isolation of tissue collagen and other types of tissue dissociation.
Collagenase also is believed to be associated with the tissue invasion progress in tumor angiogenesis, in arthritic conditions such as rheumatoid arthritis, in corneal ulceration, osteoporosis, and other diseases of connective tissue. It has been suggested that tumor angiogenesis factor (TAF) induces collagenase secretion by blood vessel endothelial cells. See Moscatelli et al., Cell 20, 343 (1980).
Rheumatoid arthritis is an inflammatory disease of the joints and connective tissue, leading to the proteolytic degradation of articular cartilage which eventually results in loss of normal joint function. The source of this destructive hydrolytic activity is the synovial cell, the primary cell lining the joint capsule. Under the stimulus of an immune reaction, proteolytic enzymes, especially collagenase, are synthesized by this cell and secreted into the joint. This high level of proteolytic activity gives rheumatoid synovium invasive capabilities which are similar to those of a malignant tumor.
The prominent role of collagenase in the degradation of the joint thus provides an important nexus for scientific investigation and the application of studies for therapeutic intervention in degenerative diseases.